WO1999058149B1

WO1999058149B1 - Controlled activation of targeted radionuclides

Info

Publication number: WO1999058149B1
Application number: PCT/US1999/009584
Authority: WO
Inventors: James C Chen
Original assignee: Light Sciences LP
Current assignee: Light Sciences LP
Priority date: 1998-05-13
Filing date: 1999-04-30
Publication date: 2000-02-03
Anticipated expiration: 2000-11-13
Also published as: WO1999058149A1; AU3969099A

Abstract

Abnormal tissue or malignant organelles within such tissue are destroyed by alpha particles emitted by radionuclide cores that are linked to the abnormal tissue. Targeted radionuclide beads each includes an alpha emitter radionuclide core (12) to which a plurality of antibody linking sites (14) are coupled. Surrounding the linking sites and radionuclide core is a polymeric shell (16) that absorbs alpha particles emitted by the core. A reagent (18) is applied to or included within the polymeric shell. Depending upon the material used for the reagent, it is activated by light of a particular waveband that is selectively applied after antibody linking sites (20) on the exterior of the shell have linked the targeted radionuclide to abnormal tissue in the body of a patient. Certain reagents are activated by light in a waveband corresponding to an absorption waveband of the reagent, while other types of reagents are activated by ultrasonic energy applied from an ultrasound source. When thus activated, the reagent causes fragmentation of the polymeric shell, enabling the alpha particles to pass into the abnormal tissue to which the radionuclide core becomes linked. The alpha particles destroy the abnormal tissue. It is also contemplated that the radionuclide core may instead emit beta particles, which though less toxic than alpha particles, can still destroy the targeted abnormal tissue.

Claims

-16- AMENDED CLAIMS

[received by the International Bureau on 20 December 1999 (20.12.99); new claims 38 and 39 added; remaining claims unchanged (2 pages)]

28. The method of Claim 27, wherein the binding agent comprises an antibody.

29. The method of Claim 26, further comprising the step of applying a binding agent to the radionuclide before the radionuclide is enclosed within the shell, said binding agent preferentially targeting and linking to the abnormal tissue at the treatment site, rather than to normal tissue.

30. The method of Claim 29, wherein the binding agent comprises an antibody.

31. The method of Claim 26, wherein the reagent is activated by one of an ultrasonic signal and a light signal.

32. The method of Claim 26, wherein the reagent comprises one of a Methylene Blue and a Bengal Rose photoreactive agent.

33. The method of Claim 26, wherein the shell comprises a polymer.

34. The method of Claim 33, wherein the shell comprises lignan.

35. The method of Claim 26, wherein the radionuclide enclosed within the shell is administered to the patient within a vascular passage and conveyed to the treatment site within a vascular fluid.

36. The method of Claim 26, wherein radionuclides enclosed within a shell in which the reagent is not activated and not retained at the treatment site are naturally excreted from the patient's body.

37. The method of Claim 26, wherein the radiation emitted by the radionuclide comprises alpha particles and the radionuclide has a half life that is substantially less than a time required for the shell to degrade within the patient's body.

38. A method for destroying abnormal tissue within a patient's body, comprising the steps of:

(a) providing a radionuclide that emits radiation having a lethal effect on the abnormal tissue;

(b) enclosing the radionuclide within a shell that blocks the radiation emitted by the radionuclide, said shell comprising a generally non-active material, and a selectively activatable reagent that when activated, is adapted to cause the shell to be breached, enabling the radiation emitted by the radionuclide to pass without blockage by the shell; -17-

(c) applying a binding agent to the shell, producing a targeted radionuclide, said binding agent being selected so that the shell preferentially links to the abnormal tissue, but not to normal tissue;

(d) administering the targeted radionuclide to a patient, said binding agent selectively linking the shell enclosing the radionuclide to the abnormal tissue; and

(e) activating the selectively activatable reagent, causing the shell to be breached, thereby enabling said radionuclide to emit the radiation, to destroy the abnormal tissue.

39. A therapeutic construct for use in destroying abnormal tissue within a patient's body, comprising:

(a) a radionuclide substance that emits radiation having a lethal effect on abnormal tissue;

(b) a shell that blocks the radiation emitted by the radionuclide, said shell enclosing the radionuclide and comprising a generally non-active material and a selectively activatable reagent that when activated, is adapted to cause the shell to be breached, enabling the radiation emitted by the radionuclide to pass without blockage by the shell; and

(c) a binding agent disposed on a surface of the shell, said binding agent being selected to preferentially link to the abnormal tissue, but not to normal tissue, said shell, said radionuclide, and said binding agent together comprising a targeted radionuclide that is adapted to be administered to a patient, bind to the abnormal tissue in the patient's body, and when the reagent is activated, expose the abnormal tissue to the radiation emitted by the radionuclide, destroying the abnormal tissue.

-18-

STATEMENT UNDER ARTICLE 19

Applicant acknowledges receipt of the International Search Report mailed 26 October 1999 and requests that the above-identified international application be amended in accordance with the attached replacement sheets. Replacement sheets 15 and 15A, containing the amendments shown below, should be substituted for original sheet 15. Applicant requests that the attached replacement sheets be published with the application.

Two claims (38 and 39) have been added to the application in the amendment shown below. New Claims 38 and 39 recite a shell comprising a generally inactive material and a selectively activatable reagent that when activated, cause the shell to be breached. These claims are fully supported by both the drawing figures (see FIGURES 1 and 4) and the specification (see page 5, line 20 to page 6, line 15). None of the prior art either teaches or suggests such a shell for encapsulating a radionuclide. Accordingly, new Claims 38 and 39, which are enabled by the specification, recite a novel and nonobvious invention. /// /// /// -19-

In the Claims:

Please add new Claims 38 and 39 as follows.

—38. A method for destroying abnormal tissue within a patient's body, comprising the steps of:

(b) enclosing the radionuclide within a shell that blocks the radiation emitted by the radionuclide, said shell comprising a generally non-active material, and a selectively activatable reagent that when activated, is adapted to cause the shell to be breached, enabling the radiation emitted by the radionuclide to pass without blockage by the shell;

(c) a binding agent disposed on a surface of the shell, said binding agent being selected to preferentially link to the abnormal tissue, but not to normal tissue, said shell, said radionuclide, -20-

and said binding agent together comprising a targeted radionuclide that is adapted to be administered to a patient, bind to the abnormal tissue in the patient's body, and when the reagent is activated, expose the abnormal tissue to the radiation emitted by the radionuclide, destroying the abnormal tissue.—